Valganciclovir in the Prevention of Cytomegalovirus Following Allogeneic Stem Cell Transplantation.

BACKGROUND: Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality after allogeneic stem cell transplantation. Valganciclovir, the valine ester of ganciclovir, has excellent oral bioavailability and has the potential to replace intravenous ganciclovir in may situations, namely CMV prophylaxis or pre-emptive therapy after allogeneic stem cell transplantation.

METHODS: From August 2002 to December 2005, 58 patients (pts) who were either CMV positive or had a seropositive donor were enrolled in a prospective trial of intravenous (IV) ganciclovir at 5 mg/Kg twice a day for one week, followed by oral valganciclovir 900 mg once daily for a total of 180 days. IV ganciclovir was started at time of engraftment. Dose adjustments of valganciclovir were made according to renal function; growth factors were allowed in the event of neutropenia. Patients were monitored with weekly antigenemia. Study endpoints included incidence of CMV reactivation and disease during the first 180 days after transplantation. For the study, viremia was defined as a positive CMV blood culture by shell vial or conventional culture. A positive antigenemia assay in pts with severe (grade III–IV) GVHD was defined as 1 positive cell on either of 2 duplicate slides. For pts with no or mild GVHD, a positive antigenemia assay was defined as 2 positive cells/slide.

RESULTS: Fifty eight pts were enrolled. The median age was 50 years (range 18–71). Twenty eight pts underwent a sibling transplant and 30 pts unrelated transplant. Twenty pts were transplanted using a reduced intensity regimen (12 received Campath-1H) and 38 pts received a standard ablative regimen with T cell depletion. There were 47 seropositive recipients and 33 seropositive donors.

Fourteen pts were not able to proceed after consenting due to screening positive antigenemia (2 pts), financial reasons (2 pts), severe gut GVHD unabling oral intake (4 pts), death (4 pts), acyclovir resistant HSV infection treated with other antiviral agents (2 pts). Forty four pts received valganciclovir. Neutropenia was observed in 7 pts, resolving in all of them. Valganciclovir was discontinued temporarily in these pts. Four of them were receiving concomitant mycophenolate mofetil. No adverse effects were otherwise reported. Nineteen pts failed to complete the study due to diagnosis of severe gut GVHD (8 pts), financial reasons (1 pt), death due to disease progression (5 pts), relapse/progression of underlying disease (5pts). Twenty six pts have completed at least 3 months of therapy and 21 pts completed 180 days. One pt experienced CMV reactivation (not taking the precribed dose). No other pt experienced CMV reactivation or disease while on therapy.

CONCLUSION: These early results suggest that valganciclovir has a role in the prevention of CMV after allogeneic stem cell transplantation. Valganciclovir is well tolerated and is an attractive oral alternative for prevention of CMV.